Quaternary salts of chlorphenoxy



V Patented Feb. 14, 1956 United States Patent'O ce 23734318 TABLE II 2734918 v V Comparison of bacteriostatic efficiencies f phenoxymeth- QUATERNARY SALTS 0F CHLORPHENOXY yl dimethyl-octylammonium chlorides and phenoxy- METHYLAMINES methyl-pyridinium chlorides Harry James Barber, Gidea Park, and Maurice Berkeley Green, Hornchurch, England, assignors to May & Baker Minimum efifwtive dilutions Limited, Dagenham, England, a company of Britain agamst No Drawing. Application September 5, 1952, Staph. B Ps.

Serial No. 308,158 aureus c0 pyocyanea Claims priority, application Great Britain May 25, 1949 Dichlomphenoxymethyl th 1- t 1 hl 2 Claims. (Cl. 260567.6) 1:512, 000 1:16, 000 1:8, 000

2: 4 Dichlorophenoxymethyl pyri- This application relates to new and valuable quaternary 5 dmum cmmde 090 salts and is a continuation-in-part of our application Serial 163,568 fil d May 22nd 1950 now abandoned atom, R1 represents a member of the class consisting of It is an object of this invention to provide valuablenew alkyl groups 113111118 more t SIX Carbon atoms, It IS one,

surface-active bactericides. It is a further object of this and R3 and ha Pb? ig defined above, P

sess remarkably high act1v1t1es as surface-active bacteriinvention to provide a narrow class of quaternary salts i p which in their bactericidal action are of outstanding merit clde? and are P E Y use as Pi l and of exceptional utility compared with Compounds of septlcs for the sterllisatlon of skin and surgical instrurelated chemical constitution ments. The exceptional utility of this particular group It is a further object to provide a process for the proof cInlm1 mds as compafed h members Wlder duction f such compounds 25 group having the aforesaid general formula s exempllfied w have prepared and have investigated the properties by the comparison of bacteriostatic efficiencies detailedm of a whole series of quaternary salts of the hitherto un- Tables I and I known phenoxymethylamines possessing the constitution: Moreover: quaternary Salts of the Present lnventlon show marked advantage over prior art compounds by R(OCH2N+R1R2R"Y virtue of the fact that their bacteriostatic eificiency is only where R represents a member of the class consisting of slightly reduced in the Presence of l O er m a illu phenyl, phenylene and naphthyl and phenyl and naphthyl trated in Tables III and IV and that, in skin sterilisation, radicals substituted by at least one of cyano, nitro, haloy are effective against both gram-Positive and g gen, lower alkyl and lower alkoxy, Y represents a member negative organisms, in particular, Pseudomonas pyocyof the class consisting of chlorine and bromine, R1, R2 anea, as illustrated in Table V.

and R3 are selected from the class consisting of individual groups and a common ring system such that when R1, R2 TABLE HI and R3 represent individual groups, R1 is a mb q Comparison of bacteriostatic efiiciency of 4-chlora-3:5- the class consisting of alkyl, aralkyl and cycloalkyl radidimelhyl phenoxymethyl-dimethyl n octylammonium R2 and R3 each represent alkyl groups contammg 40 chloride with that of other quaternary salts against not more than four carbon atoms andwhen R1, R2 and staph aureus in blood I R3 represent a common ring system they together rep- 7 t resent the residue of a heterocyclic tertiary am ne, and n Mi I m effective aim is an integer not greater than 2. tlon We have made the surprisingdiscovery that compounds 1 of the above formula in which R represents a member of f Staph.

Staph.aureus ("mm the class consisting of phenyl and lower alkyl substituted in broth in blood phenyl substituted in the nucleus by at least one chlorine v TABLE I 4-ch1oro -3:5-dimethyl-phenoxymethyl-dl- 1:1, 024, 000 1:256, 000

metliyl-n-octylammonium chloride Comparison of bacteriostaiic efiiciencies of phenoxymethfl'g g g fi gg 1 090 1 yl-dimethyl-octylammonium chlorides and phenoxy- Getyl-trimethyl ammonium bromide 1=1,024,00o 1:10, 000 methyl-dimethyl-benzyl ammonium chlorides 7 TABLE IV Minimum eflectlve dilutions flgamst- Comparison of stertllsmg etficiency of 4chl0r0-3:5-dzmethyl phenoxymethyl dimethyl n octylammonium i p can chloride with that of other quaternary salts against a B.coli in milk 4-chl0ro-3z5-dimethyl phenoxyl methyl-dimethyI-n-octylammon- Tiuie for complete sterilium chloride 111,024,000 1:10, 000 1:8, 000 I ization at concentra- 4-chloro-3z5-dimethyl phenoxytlon of 1:1,000

methyl-dimethyl-benzylammonium chloride 1:32, 000 1:4, 000 1:2, 000 4-el1loro-3-metl1yl phenoxymethyl- 4-ch1oro-3z5-dlmethyl-phenoxymethyl-di- One minute.

dimethyl-benzylammonium chlomethyl-n-octylammonium chloride ride 1:16,000 1:4,000 1:2,000 B-pheuoxyethyl-dlmethyldodecylammonlum Five minutes. Phenoxymethyldimethyl-benzylamchlori e monlum chloride 1:2, 000 1:2, 000 1:2, 000 Oetyltrimethylammonium bromide More than five minutes.

TABLE Comparision of sterilz'sing efiiciencies of phenoxymethyldimethyl-octylammonium chlorides with that of other quaternary salts against Ps.pyocyanea on skin Number of colonies oi Ps. pyocyanea remaining thirty seconds after sterilisation with a 1 percent solution 4-chloro-3z5-dlIuethyl-phenoxymethyl-dimethyl-n- Nil octylammonium chloride 2:4-dichlorophenoxymcthyl-dimethyl-n-octylammod Nil ium chloride fl-p lenoxyethyl-(limethyl-dodecylammoniuin chlo- 8 n e. Getyltrlmethylammonium bromide 13 The quaternary salts of the present invention are prepared by reacting a phenoxymethyl halide of the type ROCH2Y with a tertiary amine of the type NRiRzRs where Y, R, R1, R2 and R3 have the significance hereinbefore defined. Condensation of the phenoxymethyl halide and tertiary amine may be readily eiiected by mixing the reactants at room temperature either alone or in the presence of a suitable solvent or diluent. An

exothermic reaction takes place within a short time. After the initial reaction is over the mixture is heated to 80-100 C. for a short time and the quaternary salt isolated by filtration, crystallisation, extraction, evaporation or any other suitable method. Equimolecular proportions of the reactants are. generally used but an excess of the tertiary amine may be used if desired. The reaction solvent may be one in which the quaternary halide is soluble such as water, ethyl alcohol or chloroform or one in which the quaternary halide is insoluble such as benzene or ether. The quaternary salts may be crystallised from a mixture of ethyl acetate and chloroform.

The invention is illustrated by the following non-limitative example:

0.51 g. 3:S-dimethyl-4-chloro-phenoxymethyl chloride and 0.40 g. dimethyl-n-octylamine are mixed with 1 cc.

benzene. The temperature rises to 35 C. and a white solid separates. After 15 'minutes the mixture is heated on the steam-bath for 5 minutes under reflux. The solid is filtered off, washed with benzene and recrystallised from a mixture of chloroform and ethyl acetate, giving 0.65 g.

(3:5 dimethyl 4 chloro-phenoxymethyl) dimethyln-octyl-ammonium chloride, M. P. 1620-1635" C.; 72% yield.

In a similar manner are prepared:

Melting point, C.

3 :5 dimethyl-4-chlorophenoxymethyl-dimethyliso-octyl ammonium chloride 117-125 3 :5 climethyl-4-chlorophenoxymethyl-dimethyln-decyl ammonium chloride 152-153 3:5 dimethyl-4-chlorophenoxymethyl-dimethyllauryl ammonium chloride 143-144 3 :5 dimethyl-4-chlorophenoxymethyl-dimethylcetyl ammonium chloride 140-143 3 :5 dimethyl-4-chlorophenoxymethyl-dimethylstearyl ammonium chloride 144-147 2:4-dichlorophenoxymethyl-dimethyl n octyl ammonium chloride 2:4-dichlorophenoxymethyl-dimethyl n decyl ammonium chloride 2:4 dichlorophenoxymethyl dimethyl stearyl ammonium chloride 129-131 whereX represents at least one and at most two nuclear chlorine substituents and Z is selected from the class consisting of hydrogen and lower alkyl nuclear substituents, R1 represents a member of the class consisting of alkyl groups having more than six carbon atoms, R2 and R3 are alkyl groups containing up to four carbon atoms and Y is selected from the class consisting of chlorine and bromine.

2. A process for the production of quaternary salts of phenoxymethylamines which comprises reacting a compound of the formula with an amine of the formula NR1R2R3, where X represents at least one and at most two nuclear chlorine substituents and Z is selected from the class consisting of,

hydrogen and lower alkyl nuclear substituents, R1 represents a member of the class consisting of alkyl groups having more than six carbon atoms, R2 and R3 are alkyl groups containing up to four carbon atoms and Y is selected from the class consisting of chlorine and bromine.

References Cited in the file of this patent UNITED STATES PATENTS 2,125,901 Evans et a1 Aug. 9, 1938 2,287,464 Bock June 23, 1942 2,581,336 Hartmann et a1. Jan. 8, 1952 2,679,501 Wenner May 25, 1954 FOREIGN PATENTS 8,988 Great Britain -s of 1895 672,708 Great Britain May 28, 1952 103,324 Sweden Dec. 23, 1941 OTHER REFERENCES Tanaka: Chem. Abstracts, vol. 45, col. 5100 (1951). 

1. QUATERNARY SALTS OF PHENOXYMETHYLAMINES OF THE GENERAL FORMULA 